Project Summary: Dr. Myla Goldman is applying for a mentored patient-oriented research grant (K23) in the area of multiple sclerosis (MS). This proposal describes a research and training program designed to develop Dr. Goldman into a clinical researcher in neurology. Dr. Goldman has completed a neurology residency and a clinical neuron-immunology fellowship. To support her fellowship training, Dr. Goldman received a competitive clinical research training award from the National Multiple Sclerosis Society. Dr. Goldman's long-term career goal is to become a leader in MS clinical research, with specific expertise in motor fatigue, exercise physiology, outcome measures, and MS therapeutics. Her immediate career interests lie in the validation of an outcome measure of MS-related motor fatigue which can be used to design therapeutic trials of this disabling aspect of multiple sclerosis. She began working toward this goal during fellowship with her preliminary work validating the six-minute walk (6MW) in MS patients. Dr. Goldman's proposed research will confirm and extend her previous work validating the 6MW, which is a reliable, accessible, inexpensive, and promising outcome measure. The aims of this proposal will assess three important aspects of BMW validity- criterion validity, potential confounders, and sensitivity of the measure overtime. The proposed research is the logical next step in validating the 6MW, which will allow for outcome driven therapeutic trials of MS-related motor fatigue. In addition to having a tool to adequately test therapies for MS-related motor fatigue, this work will expand our understanding of motor fatigue, by studying its relationship to disability, subjective fatigue measures, cardiac fitness, and disease progression overtime. During the award period, Dr. Goldman will be based in the University of Virginia (UVA) Department of Neurology. UVA has a long tract record for successfully developing clinical-investigators. Dr. Goldman will be mentored by Dr. Karen Johnston in the Department of Neurology. The combined committed mentorship, didactic training, and research project of this proposal will establish her as an independent successful clinical researcher in the field of MS within the next 5 years. Public Health Relevance: MS affects 1/1000 persons in the United States and is the leading cause of non-traumatic disability in young adults. Within 12 years of disease onset, 50% of patients will require assistance with walking. Motor fatigue is one important aspect of gait dysfunction which is not captured by our bedside exam or common outcome measures. Therefore, our knowledge of its dimensions, optimal measurement, progression over time, and responsiveness to therapies remains limited.